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A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity

  1. Author:
    Carvalho, Edinilton Muniz
    Ridnour,Lisa
    Júnior, Florêncio Sousa Gouveia
    Cabral, Pedro Henrique Bezerra
    do Nascimento, Nilberto Robson Falcão
    Wink, David A
    Franco, Douglas W
    de Medeiros, Mayara Jane Campos
    de Lima Pontes, Daniel
    Longhinotti, Elisane
    de Freitas Paulo, Tércio
    Bernardes-Génisson, Vania
    Chauvin, Remi
    Sousa, Eduardo Henrique Silva
    Lopes, Luiz Gonzaga de França

  2. Author Address

    Departamento de Qu 237;mica Org 226;nica e Inorg 226;nica, Grupo de Bioinorg 226;nica, Universidade Federal do Cear 225;-UFC, P.O Box 6021, Fortaleza, CE CEP 60440-900, Brazil; CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, BP 44099, F-31077 Toulouse, Cedex 4, France; Universit 233; de Toulouse, UPS, INPT, F-31077 Toulouse, Cedex 4, France., National Cancer Institute, Cancer and Inflammation Program, Frederick, MD 21702, United States., Departamento de Qu 237;mica Org 226;nica e Inorg 226;nica, Grupo de Bioinorg 226;nica, Universidade Federal do Cear 225;-UFC, P.O Box 6021, Fortaleza, CE CEP 60440-900, Brazil., Instituto Superior de Ci 234;ncias Biom 233;dicas, Universidade Estadual do Cear 225;-UECE, Paranjana Av, 1700, Fortaleza, Cear 225; 60740-00, Brazil., Instituto de Qu 237;mica de S 227;o Carlos, Universidade de S 227;o Paulo-USP, P.O. Box 780, S 227;o Carlos, SP CEP 13566-590, Brazil., Laborat 243;rio de Qu 237;mica de Coordena 231; 227;o e Pol 237;meros (LQCPol), Instituto de Qu 237;mica, Universidade Federal do Rio Grande do Norte (UFRN), Natal CEP 59078-970, Brazil., Departamento de Qu 237;mica Anal 237;tica e F 237;sico-Qu 237;mica, Universidade Federal do Cear 225;-UFC, P.O Box 6021, Fortaleza, CE CEP 60440-900, Brazil., Departamento de Qu 237;mica Org 226;nica e Inorg 226;nica, Grupo de Bioinorg 226;nica, Universidade Federal do Cear 225;-UFC, P.O Box 6021, Fortaleza, CE CEP 60440-900, Brazil. Electronic address: eduardohss@dqoi.ufc.br., Departamento de Qu 237;mica Org 226;nica e Inorg 226;nica, Grupo de Bioinorg 226;nica, Universidade Federal do Cear 225;-UFC, P.O Box 6021, Fortaleza, CE CEP 60440-900, Brazil. Electronic address: lopeslu@dqoi.ufc.br.,
    1. Year: 2020
    2. Date: SEP
    3. Epub Date: 2020 06 20
  2. Journal: Journal of inorganic biochemistry
    1. 210
    2. Pages: 111133
  4. Type of Article: Article
  5. Article Number: 111133
  6. ISSN: 0162-0134
  1. Abstract:

    Nitric oxide (NO) and nitroxyl (HNO) have gained broad attention due to their roles in several physiological and pathophysiological processes. Remarkably, these sibling species can exhibit opposing effects including the promotion of angiogenic activity by NO compared to HNO, which blocks neovascularization. While many NO donors have been developed over the years, interest in HNO has led to the recent emergence of new donors. However, in both cases there is an expressive lack of iron-based compounds. Herein, we explored the novel chemical reactivity and stability of the trans-[Fe(cyclam)(NO)Cl]Cl2 (cyclam = 1,4,8,11-tetraazacyclotetradecane) complex. Interestingly, the half-life (t1/2) for NO release was 1.8 min upon light irradiation, vs 5.4 h upon thermal activation at 37 °C. Importantly, spectroscopic evidence supported the generation of HNO rather than NO induced by glutathione. Moreover, we observed significant inhibition of NO donor- or hypoxia-induced HIF-1a (hypoxia-inducible factor 1a) accumulation in breast cancer cells, as well as reduced vascular tube formation by endothelial cells pretreated with the trans-[Fe(cyclam)(NO)Cl]Cl2 complex. Together, these studies provide the first example of an iron-nitrosyl complex with anti-angiogenic activity as well as the potential dual activity of this compound as a NO/HNO releasing agent, which warrants further pharmacological investigation. Copyright © 2020 Elsevier Inc. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.jinorgbio.2020.111133
  3. PMID: 32619898
  4. View record in Web of Science®
  5. WOS: 000564739400018
  6. PII : S0162-0134(20)30161-6

Library Notes

  1. Fiscal Year: FY2019-2020
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